Activin A Regulates the Production of Mature Interleukin-1/3 and Interleukin-1 Receptor Antagonist in Human Monocytic Cells

Ohguchi, Masahiro; Kikkawa, Yamato; Ishihara, Yuichi; Koide, Masanori; Ueda, Nobuo; Okahashi, Nobuo; Noguchi, Toshihide; Kizaki, Masahiro; Ikeda, Yasuo; Sugino, Hiromu; Nisihara, Tatsuji

doi:10.1089/jir.1998.18.491

Cited by 73 publications

(44 citation statements)

References 41 publications

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“…Nevertheless, in vitro approaches suggest that activin A can have both pro-and anti-inflammatory actions depending on both cellular and temporal contexts . For instance, activin A stimulates the production of pro-inflammatory cytokines, prostanoids and nitric oxide synthase in activated macrophages (Nüsing & Barsig 1999), yet in other contexts it can antagonise the signalling of pro-inflammatory cytokines IL-1 and IL-6 (Brosh et al 1995, Ohguchi et al 1998. Furthermore, these studies suggest activin A release may require a direct interaction between LPS and its receptor, which is currently under investigation.…”

Section: Discussionmentioning

confidence: 97%

“…In vitro studies have revealed that activin A can act in either a pro-or anti-inflammatory manner in a number of different cell types and cell lines. Activin A is capable of antagonising IL-6-stimulated production of acute phase proteins and IL-1 bioactivity in monocytic cell lines (Brosh et al 1995, Ohguchi et al 1998, but is also capable of stimulating the production of inflammatory cytokines, prostanoids and nitric oxide synthase in activated macrophages (Nüsing & Barsig 1999). These data indicate that activin A release during inflammation, through its interaction points with other cytokines, may be important in modulating inflammatory responses.…”

Section: Introductionmentioning

confidence: 86%

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Characterisation of the rapid release of activin A following acute lipopolysaccharide challenge in the ewe

Jones

Kretser

Clarke

et al. 2004

Journal of Endocrinology

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A series of experiments were conducted in adult ewes to delineate the release profile of activin A and its relationship to other cytokines following an i.v. injection of the bacterial cell wall component, lipopolysaccharide (LPS). Following this challenge, plasma activin A increased rapidly and appeared to be released in a biphasic manner, slightly preceding the release of tumour necrosis factor-(TNF ) and before elevation of interleukin (IL)-6 and follistatin levels. The concentration of activin A was correlated with body temperature during the response to LPS. A second experiment compared cytokine concentrations in matched blood and cerebrospinal fluid (CSF) samples. This revealed that activin A was not released centrally in the CSF following a peripheral LPS injection, nor was TNF or the activin binding protein, follistatin, but IL-6 showed a robust elevation. In a third experiment, the stimulus for activin A release was examined by blocking prostaglandin synthesis. Flurbiprofen, a prostaglandin synthesis inhibitor, effectively attenuated the fever response to LPS and partly inhibited cortisol release, but the cytokine profiles were unaffected. Finally, the bioactivity of TNF and/or IL-1 was blocked using soluble receptor antagonists. These treatments did not affect the initial release of activin A, but blockade of TNF depressed the second activin peak. These studies define more rigorously the release of activin A into the circulation following acute inflammatory challenge. The response is rapid and probably biphasic, independent of prostaglandinmediated pathways and does not depend upon stimulation by TNF or IL-1. The data suggest that activin A release is an early event in the inflammatory cascade following the interaction of LPS with its cellular receptor.

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Section: Discussionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 86%

Characterisation of the rapid release of activin A following acute lipopolysaccharide challenge in the ewe

Jones

Kretser

Clarke

et al. 2004

Journal of Endocrinology

View full text Add to dashboard Cite

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“…30 However, activin A may also act as an anti-inflammatory factor regulating monocyte activation through the inhibition of interleukin-1b production and concomitant increase of IL-1 receptor antagonist expression. 31 Macrophages Macrophages, which are central effector cells of the innate immunity, have been proposed to be a cell source of activin A during the induction of a systemic inflammatory response (reviewed by Phillips et al 16 ).…”

Section: Monocytesmentioning

confidence: 99%

When versatility matters: activins/inhibins as key regulators of immunity

Alemán-Muench

Soldevila

2011

Immunol Cell Biol

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Activins and inhibins are members of the transforming growth factor-b superfamily that have been considered crucial regulators of cell processes, such as differentiation, proliferation and apoptosis, in different cell types. Initial studies about the function of activin A in the immune system focused on the regulation of hematopoiesis in the bone marrow under homeostatic and inflammatory conditions. Recent data provide a more comprehensive understanding about the role of activins/inhibins in the immune system. Novel findings included in this review point out the important requirement of activin/inhibin signaling to maintain the balance between homeostatic and inflammatory signals that are required for the optimal development and function of immune cells. The purpose of this review is to highlight the versatile nature of activins/inhibins as key regulators of both the innate and adaptive immune responses. Keywords: activin; inhibin; inflammation; immune cells; immunity; tolerance Activins and inhibins are members of the transforming growth factor-b (TGF-b) superfamily that were initially described as regulators of reproductive processes in mammals, and were first named after their positive and negative effect in the release of follicle-stimulating hormone from the pituitary gland, respectively. 1 These dimeric ligands have been shown to modulate a variety of cellular functions such as apoptosis, proliferation, differentiation, cellular migration, among others. 2,3 Activin A (bA/bA) is the best-characterized ligand of this subfamily, although there are other bioactive forms, activin B (bB/bB) and activin AB (bA/bB), which differ in their potency and cellular function. 4 Activin A is a molecule with pleiotropic functions, which shares with TGF-b the SMAD2/3 canonical signaling pathway (reviewed by Shi and Massague 5 ) but uses distinct type II (ActRIIs) and type I (ALK2, ALK4 and ALK7) receptors. [6][7][8][9] The biological function of activins can be blocked by follistatin (FS), a glycoprotein that binds activin A with high affinity, functioning as a ligand trap. 10 On the other hand, inhibins are heterodimers formed by uncommon a-and b-subunits and exist in two isoforms, inhibin A (a/bA) and B (a/bB). Inhibins have been shown to antagonize activinmediated functions by a mechanism that involves binding to b-glycan (TGFbRIII) and formation of a ternary complex with ActRIIs. As a consequence, activin type I receptors (ALK4 and ALK2) are excluded from the receptor complex, leading to the inhibition of SMADmediated signaling. 3,[11][12][13][14] Despite the fact that inhibins have been classically considered as activin antagonists, there is evidence showing that they do not always antagonize activin-mediated functions in several cell types, suggesting the existence of an independent inhibinmediated signaling pathway. 3 Compelling evidence has shown that activins also regulate various non-reproductive processes, such as mesoderm induction, liver proliferation, skin morphogenesis, erythropoiesis, bone formation, neu...

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“…At the same time, pinocytic and phagocytic activities of macrophages are enhanced greatly, and the expression of MHC molecules that are involved in presentation of antigen is increased. Previous studies have demonstrated that as an anti-inflammatory cytokine, activin A can inhibit the function of lipopolysaccharide (LPS)-activated macrophages in vitro and in vivo, and exert antagonistic effect on IL-6 and IL-11 (13)(14)(15)(16). However, the latest study reveals that insulin results in regulation of macrophage activity in response to endotoxin through the release of activin A (17), and our studies report that activin A can induce the production of inflammatory mediator NO from mouse peritoneal macrophages in vitro and activation of mouse macrophage cell line RAW264.7 cells directly (11,18).…”

Section: Introductionmentioning

confidence: 99%

A Critical Role of Activin A in Maturation of Mouse Peritoneal Macrophages in vitro and in vivo

et al. 2009

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Activin A, a multifunctional factor of the transforming growth factor-beta (TGF-) superfamily, is mainly produced by microglia and macrophages, and its anti-inflammatory and pro-inflammatory activities are both related to macrophage functions. However the direct effect of activin A on the rest macrophages in vivo remains unclear. In the present study, the results showed that activin A not only increased NO and IL-1 release, but also promoted phagocytic abilities of mouse peritoneal macrophages in vitro and in vivo, whereas it did not influence MHC I and MHC II expression. Moreover, we found that activin A significantly upregulated the expressions of CD14 and CD68, markers of mature macrophages, on the surface of macrophages in vitro and in vivo. These data suggest that activin A can induce primary macrophage maturation in vitro and in vivo, but may not trigger the acquired immune response via regulating expression of MHC molecules involved in presentation of antigen.

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Activin A Regulates the Production of Mature Interleukin-1/3 and Interleukin-1 Receptor Antagonist in Human Monocytic Cells

Cited by 73 publications

References 41 publications

Characterisation of the rapid release of activin A following acute lipopolysaccharide challenge in the ewe

Characterisation of the rapid release of activin A following acute lipopolysaccharide challenge in the ewe

When versatility matters: activins/inhibins as key regulators of immunity

A Critical Role of Activin A in Maturation of Mouse Peritoneal Macrophages in vitro and in vivo

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